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目的:进一步研究体外肿瘤抗原脉冲致敏的骨髓树突状细胞瘤苗主动免疫诱导小鼠体内抗肿瘤免疫应答,并观察其抵抗野生性肿瘤攻击的免疫保护作用及对荷瘤小鼠模型的免疫应答。方法:采用本室建立的骨髓树突状细胞分离与细胞因子体外扩增培养方法,并在体外经灭活NS1骨髓瘤细胞及其裂解产物脉冲刺激后直接作为疫苗,然后进行免疫预防与治疗的在体动物实验。结果:可从1只小鼠股骨中获得(3~5)×105个树突状细胞(DC),其纯度为95%以上,对混合T淋巴细胞具有强刺激活性。主动免疫同系健康BALB/C小鼠的试验显示,DC疫苗能诱导抗原特异的细胞毒性T淋巴细胞(CTL)活性,免疫1次的动物首次受到肿瘤攻击后诱发肿瘤形成率为0%,再次攻击的肿瘤形成率为20%;而免疫3次的动物两次攻击的肿瘤形成率皆为0%。主动免疫治疗同种荷瘤动物的试验表明,DC疫苗也能抑制肿瘤生长,荷瘤动物存活率提高及生存期明显延长。结论:肿瘤抗原体外致敏的树突状细胞能诱导宿主体内的抗肿瘤免疫保护性反应,且对荷瘤模型动物具有明显的免疫治疗作用。
OBJECTIVE: To further study the anti-tumor immune response induced by pulse immunization with tumor antigen in vitro in bone marrow-derived dendritic cell tumor vaccines in mice, and to observe the immune protection against wild tumor challenge and immunity to tumor-bearing mouse models. answer. METHODS: The method for the isolation and expansion of cytokines in vitro was established by using the method established in this laboratory. In vitro, the NS1 myeloma cells and their lysates were pulsed and stimulated directly to serve as a vaccine, followed by immunoprevention and treatment. In vivo animal experiments. RESULTS: (3 ~ 5) × 105 dendritic cells (DC) were obtained from the femur of 1 mouse. The purity of the dendritic cells was more than 95%, and they had strong stimulatory activity on mixed T lymphocytes. Active immunization with homozygous healthy BALB/C mice showed that the DC vaccine could induce antigen-specific cytotoxic T lymphocyte (CTL) activity. Once the animals that were immunized for the first time were challenged by the tumor, the tumor formation rate was 0%. The tumorigenesis rate was 20%; in animals that were immunized three times, the tumor formation rate was 0% for both attacks. Active immunotherapy of the same tumor-bearing animals showed that DC vaccine can also inhibit tumor growth, and the survival rate and survival time of tumor-bearing animals were significantly prolonged. CONCLUSION: Dendritic cells sensitized by tumor antigens in vitro can induce anti-tumor immune protective responses in the host, and have significant immunotherapy effects on tumor-bearing model animals.